The efficiency of gut absorption is essential for good food conversion. Gut adsorption is largely determined by the gut surface, which is a function, amongst others, of the length of the gut and the height of the villi. In cases where an operative removal of a part of the gut is necessary, as in the case of cancer or Crohn's disease, this may result in decreased gut adsorption, resulting in insufficient food conversion and a shortage of nutrients, dehydration and even potentially lethal metabolic changes. These syndromes caused by the extensive resection of the small intestine are known as “Short Bowel Syndrome.”
Several methods have been proposed to improve the post-operational adaptation of, and to enhance, the gut absorption in patients with Short Bowel Syndrome. U.S. Pat. No. 5,288,703 discloses that both growth hormone and insulin-like growth factor have a positive effect on gut absorption in mammals. This positive effect can be enhanced by the administration of glutamine or a glutamine equivalent. Administration of glutamine and growth hormone results in an increase of the villi length (Gu et al., 2001; Zhou et al., 2001). U.S. Pat. No. 5,972,887 demonstrated a reversal of the reduced intestinal mucosal mass and absorptive function in patients by the administration of low doses of exogenous Hepatocyte Growth Factor. In addition, the glucagon-like peptides GLP-1 and GLP-2 have been used with positive results. Studies on laboratory animals (Scott et al., 1998), as well as on humans (Jeppesen et al., 2001), showed a positive correlation between an increase in concentration of GLP-2 and an improvement of the intestinal adaptation. Short Bowel patients, from whom the ileum has been removed, show a decrease in food-induced secretion of GLP-2 (Jeppesen et al., 1999). Those patients, especially, can be treated successfully with GLP-2. It has been shown that leptin also has a positive effect on intestinal adaptation in a rat model (Pearson et al., 2001).
A lot of interest has been paid to the effect of Epidermal Growth Factor (EGF, urogastron). EGF is a relatively acid stable hormone that is produced in the salivary and the Brunner's glands. It is found in a wide variety of external secretions, as well as in blood and amniotic fluid (Marti et al., 1989). The molecular weight of mature human EGF is 6.2 kDa (Carpenter et al., 1991). EGF is phylogenetically strongly conserved and is strongly cross-reactive between different species.
It is known that EGF increases the absorption of H2O, Na+, Cl− and glucose in a rabbit model (Opleta-Madsen et al., 1991). Moreover, EGF is stimulating the elongation of the villi. This results in an increase of the apical surface and a general increase in absorption of nutrients (Hardin et al., 1999). Absorption of carbohydrates is further facilitated by the EGF-stimulated secretion of pancreatic amylase (Piiper et al., 1994).
Several studies have shown a positive effect of the application of EGF in experimental animal models for Short Bowel Syndrome (Helmrath et al., 1988; Chaet et al., 1994; O'Loughlin et al, 1994; Swaniker et al., 1996; Lukish et al., 1997; Dunn et al., 1997).
EGF-mediated effects after intestinal resection are strongly dose dependent; up to a certain limit, the adaptation increases with increasing doses. In intestinal studies, the normal dose is situated between 30 and 300 μg/kg body weight/day. Systemic, as well as enteral, applications seem effective. However, systemic application may be unwanted for possible side effects; several neoplasmas do have EGF receptors and a general increase in EGF concentration in the blood might stimulate the formation of tumors. Enteral application of EGF, however, is less efficient as pepsin can process mature EGF into a truncated form that has only 25% of the initial biological activity (Playford et al., 1995).